Year-end Sale % OFF 
Abstract
A plague vaccine with a fusion cassette of YscF, F1, and LcrV encoding genes in an adenovirus-5 vector (rAd5-YFV) is evaluated for efficacy and immune responses in mice. Two doses of the vaccine provides 100% protection when administered intranasally against challenge with Yersinia pestis CO92 or its isogenic F1 mutant in short- or long- term immunization in pneumonic/bubonic plague models. The corresponding protection rates drop in rAd5-LcrV monovalent vaccinated mice in plague models. The rAd5-YFV vaccine induces superior humoral, mucosal and cell-mediated immunity, with clearance of the pathogen. Immunization of mice with rAd5-YFV followed by CO92 infection dampens proinflammatory cytokines and neutrophil chemoattractant production, while increasing Th1- and Th2-cytokine responses as well as macrophage/monocyte chemo-attractants when compared to the challenge control animals. This is a first study showing complete protection of mice from pneumonic/bubonic plague with a viral vector-based vaccine without the use of needles and the adjuvant.
Highlights
Yersinia pestis, the causative agent of plague, is a Tier-1 select agent and a re-emerging human pathogen[1,2]
We have previously shown that a single dose administration of the rAd5-YFV vaccine (8.0 × 109 v.p.) by the i.n. route to mice provided complete protection against bubonic plague, while 60% protection was achieved against pneumonic plague (i.n. challenge)[24]
To improve efficacy of the rAd5-YFV vaccine against pneumonic plague, our first attempt was to increase the i.n. immunization dose from 8.0 × 109 v.p. to 1.2 × 1010 v.p., and use vaccination regimen of either 1 dose or 2 doses in mice (Fig. 1a, b)
Summary
The causative agent of plague, is a Tier-1 select agent and a re-emerging human pathogen[1,2]. There have been three plague worldwide pandemics, which were responsible for over 200 million deaths[3]. The most recent large outbreak of plague (2017–2018) occurred in Madagascar which resulted in ~2400 cases and ~200 deaths[4]. Over 75% of the plague cases were pneumonic in this outbreak[5]. Most cases of plague globally are bubonic in nature, which has a lower case-fatality rate and longer disease course than pneumonic plague[3]. On the other hand, has a shorter disease course and an almost 100% fatality rate if not treated with appropriate antibiotics within 24 h of symptom onset, making it an urgent public health priority[6]. Vallès et al recently emphasized the importance of developing a clear roadmap on plague vaccines based on the current knowledge gaps[7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
